High prevalence of carbapenem-resistant Enterobacterales (CRE) in human samples from Nigeria: A systematic review and meta-analysis.

Objectives: The rise in Carbapenem-resistant Enterobacterales (CRE) is perturbing. To curb the menace of CRE, a comprehensive understanding of its prevalence and epidemiology is crucial. As varying reports abound, the true prevalence of CRE in Nigeria remains unknown. Here, we conducted a systematic review and meta-analysis following standard guidelines to assess the situation of CRE in Nigeria. Methods: We searched electronic databases including Pubmed, ScienceDirect, Scopus, Web of Science, and Google Scholar for articles providing information on CRE in Nigeria. The data gathered were analyzed using OpenMeta Analyst and Comprehensive Meta-Analysis software. The random-effect model was employed to calculate pooled resistance to carbapenem antibiotics. Results: From 321 retrieved records, 57 were finally included. The studies were predominantly from the South-West region (n = 19). Escherichia coli and Klebsiella pneumoniae were the most frequently tested Enterobacterales among the included studies. The pooled prevalence estimate for imipenem resistance among CRE was 11.2 % (95 % CI: 7.9-15.7). Meropenem resistance had an estimate of 13.5 % (95 % CI: 9.1-19.6), whereas ertapenem and doripenem were estimated at 17.0 % (95 % CI: 9.9-27.7) and 37.9 % (95 % CI: 15.0-67.8), respectively. High heterogeneity (I 2 >85 %, p < 0.001) was observed for the estimates. The highest resistance rate to imipenem (28.4 %), meropenem (37.2 %) and ertapenem (46.5 %) were observed for the South-South region. Based on specific CRE genera, Morganella sp. was the most resistant (37.0 %) while Escherichia sp. was the least (9.4 %). Our analyses also revealed a progressive increase in resistance to carbapenem antibiotics over the years. Conclusion: This study highlights carbapenem resistance as a concern in Africa's most populous nation, underscoring the need for proactive measures to address and mitigate the threat of CRE.

Role of MicroRNAs in Inflammatory Joint Diseases: A Review.

Inflammatory arthritis commonly initiates in the soft tissues lining the joint. This lining swells, as do the cells in it and inside the joint fluid, producing chemicals that induce inflammation signs such as heat, redness, and swelling. MicroRNA (miRNA), a subset of non-coding small RNA molecules, post-transcriptionally controls gene expression by targeting their messenger RNA. MiRNAs modulate approximately 1/3 of the human genome with their multiple targets. Recently, they have been extensively studied as key modulators of the innate and adaptive immune systems in diseases such as allergic disorders, types of cancer, and cardiovascular diseases. However, research on the different inflammatory joint diseases, such as rheumatoid arthritis, gout, Lyme disease, ankylosing spondylitis, and psoriatic arthritis, remains in its infancy. This review presents a deeper understanding of miRNA biogenesis and the functions of miRNAs in modulating the immune and inflammatory responses in the above-mentioned inflammatory joint diseases. According to the literature, it has been demonstrated that the development of inflammatory joint disorders is closely related to different miRNAs and their specific regulatory mechanisms. Furthermore, they may present as possible prognostic and diagnostic biomarkers for all diseases and may help in developing a therapeutic response. However, further studies are needed to determine whether manipulating miRNAs can influence the development and progression of inflammatory joint disorders.

Designing mRNA- and Peptide-Based Vaccine Construct against Emerging Multidrug-Resistant Citrobacter freundii: A Computational-Based Subtractive Proteomics Approach.

Background and Objectives: Citrobacter freundii (C. freundii) is an emerging and opportunistic Gram-negative bacteria of the human gastrointestinal tract associated with nosocomial and severe respiratory tract infections. It has also been associated with pneumonia, bloodstream, and urinary tract infections. Intrinsic and adaptive virulence characteristics of C. freundii have become a significant source of diarrheal infections and food poisoning among immune-compromised patients and newborns. Impulsive usage of antibiotics and these adaptive virulence characteristics has modulated the C. freundii into multidrug-resistant (MDR) bacteria. Conventional approaches are futile against MDR C. freundii. Materials and Methods: The current study exploits the modern computational-based vaccine design approach to treat infections related to MDR C. freundii. A whole proteome of C. freundii (strain: CWH001) was retrieved to screen pathogenic and nonhomologous proteins. Six proteins were shortlisted for the selection of putative epitopes for vaccine construct. Highly antigenic, nonallergen, and nontoxic eleven B-cell, HTL, and TCL epitopes were selected for mRNA- and peptide-based multi-epitope vaccine construct. Secondary and tertiary structures of the multi-epitope vaccine (MEVC) were designed, refined, and validated. Results: Evaluation of population coverage of MHC-I and MHC-II alleles were 72% and 90%, respectively. Docking MEVC with TLR-3 receptor with the binding affinity of 21.46 (kcal/mol) occurred through the mmGBSA process. Further validations include codon optimization with an enhanced CAI value of 0.95 and GC content of about 51%. Immune stimulation and molecular dynamic simulation ensure the antibody production upon antigen interaction with the host and stability of the MEVC construct, respectively. Conclusions: These interpretations propose a new strategy to combat MDR C. freundii. Further, in vivo and in vitro trials of this vaccine will be valuable in combating MDR pathogens.